Purkinje cells show two distinct forms of electrophysiological activity:

Simple spikes occur at rates of 17 – 150 Hz (Raman and Bean, 1999), either spontaneously or when Purkinje cells are activated synaptically by the parallel fibers, the axons of the granule cells.

Complex spikes are slow, 1–3 Hz spikes, characterized by an initial prolonged large-amplitude spike, followed by a high-frequency burst of smaller-amplitude action potentials. They are caused by climbing fiber activation and can involve the generation of calcium-mediated action potentials in the dendrites. Following complex spike activity, simple spikes can be suppressed by the powerful complex spike input.[4]

The Purkinje cell protein 4 (PCP4) is markedly immunoreactive in the Purkinje cells of the human cerebellum. From top to bottom 40X, 100X and 200X microscopic magnifications. The immunohistochemistry was performed based on published methods.[5]

Purkinje cells show spontaneous electrophysiological activity in the form of trains of spikes both sodium-dependent and calcium-dependent. This was initially shown by Rodolfo Llinas (Llinas and Hess (1977) and Llinas and Sugimori (1980). P-type calcium channels were named after Purkinje cells, where they were initially encountered (Llinas et al. 1989), which are crucial in cerebellar function. We now know that activation of the Purkinje cell by climbing fibers can shift its activity from a quiet state to a spontaneously active state and vice versa, serving as a kind of toggle switch.[6] These findings have been challenged by a study suggesting that such toggling by climbing-fiber inputs occurs predominantly in anaesthetized animals and that Purkinje cells in awake behaving animals, in general, operate almost continuously in the upstate.[7] But this latter study has itself been challenged [8] and Purkinje cell toggling has since been observed in awake cats.[9] A computational model of the Purkinje cell has shown intracellular calcium computations to be responsible for toggling.[10]

Findings have suggested that Purkinje cell dendrites release endocannabinoids that can transiently downregulate both excitatory and inhibitory synapses.[11] The intrinsic activity mode of Purkinje cells is set and controlled by the sodium-potassium pump.[12] This suggests that the pump might not be simply a homeostatic, "housekeeping" molecule for ionic gradients. Instead, it could be a computation element in the cerebellum and the brain.[13] Indeed, a mutation in the Na+-K+ pump causes rapid onset dystonia parkinsonism; its symptoms indicate that it is a pathology of cerebellar computation.[14] Furthermore, using the poison ouabain to block Na+-K+ pumps in the cerebellum of a live mouse induces ataxia and dystonia.[15] Numerical modeling of experimental data suggests that, in vivo, the Na+-K+ pump produces long quiescent punctuations (>> 1 s) to Purkinje neuron firing; these may have a computational role.[16]

The Purkinje layer of the cerebellum, which contains the cell bodies of the Purkinje cells and Bergmann Glia, express a large number of unique genes.[17] Purkinje-specific gene markers were also proposed by comparing the transcriptome of Purkinje-deficient mice with that of wild-type mice.[18] One illustrative example is the Purkinje cell protein 4 (PCP4)knockout mice, which exhibit impaired locomotor learning and markedly altered synaptic plasticity in Purkinje neurons.[5][19] PCP4 accelerates both the association and dissociation of calcium (Ca2+) with calmodulin (CaM) in the cytoplasm of Purkinje cells, and its absence impairs the physiology of these neurons.[5][19][20][21]

In humans, Purkinje cells can be harmed by a variety causes: toxic exposure, e.g. to alcohol or lithium; autoimmune diseases; genetic mutations causing spinocerebellar ataxias, Unverricht-Lundborg disease, or autism; and neurodegenerative diseases that are not known to have a genetic basis, such as the cerebellar type of multiple system atrophy or sporadic ataxias.

Some domestic animals can develop a condition where the Purkinje cells begin to atrophy shortly after birth, called Cerebellar abiotrophy. It can lead to symptoms such as ataxia, intention tremors, hyperreactivity, lack of menace reflex, stiff or high-stepping gait, apparent lack of awareness of foot position (sometimes standing or walking with a foot knuckled over), and a general inability to determine space and distance.[22] A similar condition known as cerebellar hypoplasia occurs when Purkinje cells fail to develop in utero or die off before birth.

The genetic conditions Ataxia Telangiectasia and Niemann Pick disease Type C, as well as cerebellar essential tremor, involve the progressive loss of Purkinje cells. In Alzheimer's disease, we sometimes see spinal pathology as well as loss of dendritic branches of the Purkinje cells.[23] Purkinje cells can also be damaged by the rabies virus as it migrates from the site of infection in the periphery to the central nervous system [24]